Mutational signatures: emerging concepts, caveats and clinical applications

Whole-genome sequencing has brought the cancer genomics community into new territory. Thanks to the sheer power provided by the thousands of mutations present in each patient's cancer, we have been able to discern generic patterns of mutations, termed 'mutational signatures', that arise during tumorigenesis. These mutational signatures provide new insights into the causes of individual cancers, revealing both endogenous and exogenous factors that have influenced cancer development. This Review brings readers up to date in a field that is expanding in computational, experimental and clinical directions. We focus on recent conceptual advances, underscoring some of the caveats associated with using the mutational signature frameworks and highlighting the latest experimental insights. We conclude by bringing attention to areas that are likely to see advancements in clinical applications. Mutational signatures can provide insights into the origins and vulnerabilities of specific cancers, and have potential for clinical utility. This Review highlights recent developments in the field, providing insights into practical issues and challenges in mutational signature analysis.

Automated summary

Whole-genome sequencing has enabled the identification of mutational signatures in cancer, shedding light on the causes of individual cancers. Progress has been made in computational, experimental, and clinical directions, but caution is advised in utilizing mutational signature frameworks. Recent developments in the field provide insights into practical issues and challenges in mutational signature analysis for potential clinical applications.